A Phase II Study Using Post-Transplant Cyclophosphamide (PTC) As Graft Versus Host Disease (GVHD) Prophylaxis in Patients Undergoing HLA Matched Sibling Donor Stem Cell Transplant (SCT) for Severe Aplastic Anemia (SAA)

Abstract 4199

Between September 2010 and June 2012, 15 patients with SAA underwent HLA identical sibling donor SCT using post transplant cyclophosphamide for GVHD prophylaxis. The conditioning regimen consisted of Inj Fludarabine 30 mg/m²/day from day -7 to -2 and Inj Cyclophosphamide 50 mg/kg IV on days -3 and -2. Total Body irradiation (TBI) 200 cGy as single fraction was added on day -1 from December 2011 because of concern regarding graft failure. GVHD prophylaxis consisted of Inj Cyclophosphamide administered at 50 mg/kg/day IV on day +3 and +4 post SCT. G-CSF mobilized peripheral blood stem cells (PBSC) was the graft source.

There were 10 males and 5 females with a median age of 25.9 years (range: 8 – 42). The median time from diagnosis to SCT was 7.5 months (range: 2 – 36). All had 6/6 HLA matched sibling donors except 1 who had a 9/10 matched family donor. The median PBSC cell dose infused was 5.4 × 10⁸ MNC/Kg (range: 2.4 – 8.5) and 9.58 × 10⁶CD34/Kg (range: 5.4 – 17.2). Thirteen patients engrafted (86.6%) with a median time to ANC >0.5 × 10⁹/L of 15.4 days (range: 15–17) and Platelet count >20 × 10⁹ of 16.6 days (range: 12–32). Grade II –IV acute GVHD occurred in 3 patients (23%) at 42, 49 and 68 days post SCT. GVHD was grade II in 2 patients and grade IV in 1 patient. Two responded to a combination of cyclosporine and prednisolone while one patient with grade IV GVHD expired with refractory GVHD at median time of 64 days post SCT. Of the 11 evaluable patients, 4 (36.3%) developed chronic GVHD which was limited in all. Two patients who developed de novo chronic GVHD were managed with prednisolone alone. Overall 7 patients (46.6%) have not required any immunosuppression after SCT while 3 have required immunosuppressive therapy for 114, 127 and 225 days respectively At a median follow up of 11 months (range: 1 – 22), 11 (73.3%) are alive and well including 7 patients who did not require any immunosuppressive therapy following SCT.

In conclusion, the use of post transplant cyclophosphamide as GVHD prophylaxis following sibling donor transplant for SAA is associated with low rates of GVHD. What makes it more attractive is the fact that 46% did not require any immunosuppression post SCT. Larger studies are required to understand the utility of this prophylaxis in sibling donor transplants for aplastic anemia.

This trial is registered in the Clinical Trials Registry India - CTRI/2010/091/001480.